Summary of Work: Dr. Yogi Nagai joined LSB in March 1996 to work on the project with us. The project studies intracerebral blood flow velocity and resistance, and carotid blood flow velocity using doppler ultrasonography in BLSA participants. The goal is to determine how these factors, which are associated with cerebrovascular diseases, change with age. It complements the studies of Drs. Lakatta and Fleg in the LCS on arterial stiffness, by exploring the effects of stiffness on an end organ (the brain). A number of analyses have been completed: (1)To determine whether intimal-medial thickness of the common carotid artery (CCA IMT), a proposed index of atherosclerosis, is increased in asymptomatic older subjects with an ischemic ST-segment response to treadmill exercise. Intimal medial thickness (IMT) of the common carotid artery (CCA) increases with age concomitant with CCA dilatation, elevation of systolic blood pressure and differently by gender. The change in IMT is exacerbated by the presence of coronary heart disease (CHD). In fact, individuals with asymptomatic CHD show wall thickening that is less than observed in symptomatic CHD and greater than healthy controls. Each 0.1 mm increase in IMT was independently associated with a 1.78 fold (95% CI 1.34-2.36, p<0.0001) increased risk for concordant positive exercise tests or manifest CAD. (2) A new index, the decay index (DI), was developed to examine changes in flow velocity during late systole. It is obtained from the Doppler waves recorded on videotapes using a newly developed computer program. DI is directly associated with aortic stiffness and to a lesser extent with arterial peripheral resistance. It was found to be independently related to age and CHD, as compared to other measures of carotid stiffness. (3) AGI and ultrasonographical indices of elasticity express different characteristic of vascular stiffness. Augmentation index (AGI)(r=.38, p=.000) and Ep increased with age, DC(r=-.43, p=.000) and CC(r=-.25, p=.021) decreased with age, while YM did not change with age. AGI did not significantly correlate with the ultrasonographical indices, though Ep and YM had significant correlations with AGI after controlling for age (r2=.23, r2=.18, respectively). The findings suggest that both the AGI and ultrasonographic measurements should give a better understanding of arterial changes with age, than either measurement alone. Further analyses are underway to examine the effects of estrogen on arterial elasticity in postmenopausal women, and to compare flow velocities in CCA, internal carotid and middle cerebral arteries in healthy women and men across the adult life span.